1.Mechanism of total salvianolic acid improving myeloid macrophage infiltration in liver cancer bearing mice by regulating TLR4/MyD88/NF-κB pathway
Yunan DU ; Zhibo DANG ; Xiqian ZHANG ; Gaofeng TAN ; Honglin LI ; Yunfei JIA
Chinese Journal of Immunology 2025;41(11):2624-2630
Objective:To investigate the impacts of total salvianolic acid(TSA)on macrophage polarization and mesenchymal macrophage infiltration in liver cancer bearing mice by regulating the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods:Mice were randomly separated into liver cancer group,TSA low concentra-tion group,TSA medium concentration group,TSA high concentration group,TSA high concentration+TLR4 inhibitor(TAK242)group and control group,with 12 mice in each group.Except for control group,mice in all other groups were injected subcutaneously into the right axilla to construct liver cancer models by intraperitoneal transmission of third-generation H22 cell suspension.After suc-cessful modeling,administration was carried out once a day for 2 weeks.Changes in tumor weight,tumor volume,spleen index and thymus index were detected.Immunofluorescence was applied to detect proportions of CD86 and CD206 positive cells in tumor tissue.ELISA was applied to detect levels of inducible nitric oxide synthase(iNOS),IL-6 and IL-10 in tumor tissues.Flow cytometry was ap-plied to detect proportion of CD11b+F4/80+in tumor tissue.Western blot was applied to detect TLR4,p-NF-κB P65 and MyD88 pro-teins in tumor tissue.The life quality and survival rate of mice were observed.Results:Compared with control group,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were reduced in liver cancer group,while proportion of CD206 positive cells and level of IL-10 in tumor tissue were increased(P<0.05).Compared with liver cancer group,tumor weight and volume of mice in TSA low,medium,high concentration groups were decreased,while survival rate,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were increased,proportion of CD206 positive cells,level of IL-10,and proportion of CD11b+F4/80+in tumor tissue decreased(P<0.05).TAK242 reversed the effects of high concentration TSA on macrophage polarization and myeloid macrophage infiltration in liver cancer bearing mice.Conclusion:TSA may promote M1 polari-zation of macrophages in liver cancer bearing mice and inhibit myeloid macrophage infiltration by activating the TLR4/MyD88/NF-κB pathway.
2.Mechanism of total salvianolic acid improving myeloid macrophage infiltration in liver cancer bearing mice by regulating TLR4/MyD88/NF-κB pathway
Yunan DU ; Zhibo DANG ; Xiqian ZHANG ; Gaofeng TAN ; Honglin LI ; Yunfei JIA
Chinese Journal of Immunology 2025;41(11):2624-2630
Objective:To investigate the impacts of total salvianolic acid(TSA)on macrophage polarization and mesenchymal macrophage infiltration in liver cancer bearing mice by regulating the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods:Mice were randomly separated into liver cancer group,TSA low concentra-tion group,TSA medium concentration group,TSA high concentration group,TSA high concentration+TLR4 inhibitor(TAK242)group and control group,with 12 mice in each group.Except for control group,mice in all other groups were injected subcutaneously into the right axilla to construct liver cancer models by intraperitoneal transmission of third-generation H22 cell suspension.After suc-cessful modeling,administration was carried out once a day for 2 weeks.Changes in tumor weight,tumor volume,spleen index and thymus index were detected.Immunofluorescence was applied to detect proportions of CD86 and CD206 positive cells in tumor tissue.ELISA was applied to detect levels of inducible nitric oxide synthase(iNOS),IL-6 and IL-10 in tumor tissues.Flow cytometry was ap-plied to detect proportion of CD11b+F4/80+in tumor tissue.Western blot was applied to detect TLR4,p-NF-κB P65 and MyD88 pro-teins in tumor tissue.The life quality and survival rate of mice were observed.Results:Compared with control group,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were reduced in liver cancer group,while proportion of CD206 positive cells and level of IL-10 in tumor tissue were increased(P<0.05).Compared with liver cancer group,tumor weight and volume of mice in TSA low,medium,high concentration groups were decreased,while survival rate,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were increased,proportion of CD206 positive cells,level of IL-10,and proportion of CD11b+F4/80+in tumor tissue decreased(P<0.05).TAK242 reversed the effects of high concentration TSA on macrophage polarization and myeloid macrophage infiltration in liver cancer bearing mice.Conclusion:TSA may promote M1 polari-zation of macrophages in liver cancer bearing mice and inhibit myeloid macrophage infiltration by activating the TLR4/MyD88/NF-κB pathway.
3. Research on serum metabolic markers of menopausal syndrome based on
Caifeng DU ; Yunan MAO ; Jia GAO ; Juan WANG ; Xiaoye LI ; Hongqi LIU ; Junsheng TIAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(9):961-968
AIM: To find specific metabolic markers for women entering peri-menopausal period and patients with menopausal syndrome based on
4.Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia.
Bing-Jie GUO ; Yi RUAN ; Ya-Jing WANG ; Chu-Lan XIAO ; Zhi-Peng ZHONG ; Bin-Bin CHENG ; Juan DU ; Bai LI ; Wei GU ; Zi-Fei YIN
Journal of Integrative Medicine 2023;21(5):474-486
OBJECTIVE:
Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment.
METHODS:
The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway.
RESULTS:
According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway.
CONCLUSION
JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals
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Mice
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Humans
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Carcinoma, Hepatocellular/genetics*
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beta Catenin/pharmacology*
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Liver Neoplasms/genetics*
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Drugs, Chinese Herbal/therapeutic use*
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RNA, Messenger/therapeutic use*
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Cell Line, Tumor
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Cell Proliferation
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Cell Movement
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Gene Expression Regulation, Neoplastic
5.Study on calculation method of internal and external fluid capacity of human cells based on bioimpedance spectroscopy.
Li KE ; Jiawei XU ; Yunan ZHAO ; Qiang DU ; Haiming LU
Journal of Biomedical Engineering 2019;36(4):643-648
Bioelectrical impedance measurement technology is a non-invasive detection technology for extracting human physiological and pathological information. The analysis method of the relationship between bioimpedance and human physiological parameters is an important part of this technology. In order to calculate the internal and external liquid volume of human cells more accurately, based on the Moissl equation for calculating the internal and external fluid volume of human cells, a segmented human bioimpedance spectrum measurement model and an improved calculation method of intracellular and external fluid capacity were proposed. The measurement and calculation experiments of the intracellular and extracellular fluid volume before and after the human body's water intake were designed and compared with the Moissl calculation method. The results show that the improved calculation method can calculate the intracellular and extracellular fluid volumes more effectively, and the relative error is less than 5%, which may provide new ideas or more accurate methods for the analysis of human body components, facilitating the diagnosis and treatment of diseases.
Body Water
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Electric Impedance
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Extracellular Fluid
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Humans
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Intracellular Fluid
6.New Perspectives of Chinese Medicine: Philosophic Analysis of Its Advantage-characters and Its Development in Future
Lijun DU ; Yunan ZHAO ; Fan LEI ; Weidong XIE ; Jun LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(9):1435-1442
To today of its development,the tenacious vitalities of traditional Chinese medicine (TCM) beyond doubt.From this point of view,it has a positive meaning to analyze and understand TCM,from which to find its advantages and characteristics for better improvement and development of TCM-theory,so that better for the benefit of mankind.Therefore,they were discussed from the perspective of philosophy of science with the conclusion as follows:1.It is a major current Chinese medicine theory Features that the conceptual system of metaphysical nature made the organic combination of syndrome differentiation and treatment,and the Chinese herbal medicines and other therapy as a means of feedback to verify and correct TCM's theory.2.The theory of current Chinese medicine is different from the theory of TCM,because its theoretical deduction and its argument are different from the focus of ancient Chinese medicine.These development and innovation in current Chinese medicine needs to be studied and summarized.3.Chinese medicine and Western medicine should be parallel to the two medical theory systems,both of which enrich the prevention and treatment of diseases.4.As an independent medical theory system,Chinese medicine theory must also need to develop and even revolution.And this process depends on the overall level of development and improvement of science and technology.
7.Differentiation of human umbilical cord blood-derived mesenchymal stem cells into chondroblast and osteoblasts.
Yanqiu YU ; Haiqin REN ; Wei YUN ; Yunan JIN ; Kuni LI ; Lili DU
Journal of Biomedical Engineering 2008;25(6):1385-1389
Samples of healthy and full-term human umbilical cord blood samples were obtained asceptically. Mesenchymal stem cells (MSCs) were isolated by lymphocyte separation medium, and were characterized morphologically by fluorescence-activated cell sorting analysis. Differentiation of chondroblast and osteoblast was induced by 10 ng/ml TGF-beta, 100 ng/ml insulin and 10(-7) mol/L decaesadril, 6.25 microg/ml siderophilin, 10 mmol/L beta-sodium glycerophosphate, 50 microg/ml antiscorbic acid, respectirely; the aim was to investigate the potentiality of differentiation. Umbilical cord blood-derived MSCs were stained positive for MSCs marker CD13, CD90, CD166, CD73, CD44 and HLA-AB, but were negative for hematopoietic stem cell marker CD45, CD34 and HLA-DR. After 21 days induction, Toluidine Blue staining and von-Kossa staining were positive. Immunocytochemistry showed that Collagen II expressed in the induced cells. The results demonstrated that mesenchymal stem cells can be isolated from human umbilical cord blood and differentiated into chondroblasts and osteoblasts in vitro.
Cell Differentiation
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Cell Separation
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Cells, Cultured
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Chondrocytes
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cytology
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Fetal Blood
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cytology
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Humans
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Mesenchymal Stromal Cells
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cytology
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Osteoblasts
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chemistry
8.Comparison of berberine between normal and febrile rats——pharmacokinetic study of antifebrile complex YL2000
Yunan ZHAO ; Dongming XING ; Yi DING ; Wen JIN ; Wei WANG ; Fan LEI ; Lijun DU ;
Chinese Pharmacological Bulletin 2003;0(10):-
AIM To explore pharmacokinetics of Berberine in YL2000 in normal and febrile rats. METHODS The levels of Berberine in plasma were measured through HPLC and secondary parameters were obtained by fitting the dose time data of Berberine making use of 3P87 programme. RESULTS In normal and febrile rats, the plasma concentration of Berberine was peaked at (3 4?0 3) h vs (0 3?2 1) h( P
9.Isolation and differentiation of stem cells derived from human placenta into cardiomyocytes
Yanqiu YU ; Kun LI ; Yunan JIN ; Wei YUN ; Lili DU ; Xiaomei LU ; Haiqin REN
Chinese Journal of Pathophysiology 1989;0(05):-
AIM: To isolate the stem cells from human placenta and induce them into cardiomyocytes. METHODS: Stem cells were isolated from human placenta and characterized by morphologic analysis. The “hanging drop” methods were used to inducte stem cells into cardiomyocytes. The expressions of atrial natriuretic factor(Anf) and ?-myosin heavy chain(?-MHC) genes were analyzed by RT-PCR. RESULTS: Stem cells derived from human placenta were self-renewed and differentiated into cardiomyocytes in vitro. RT-PCR showed that Anf and ?-MHC genes were expressed in the “beating cells”.CONCLUSION: Human placenta is an abundant source of stem cells.

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